Pregnancy level of estradiol attenuated virus-specific humoral immune response in H5N1-infected female mice despite inducing anti-inflammatory protection
Estradiol, a major female steroid produced during pregnancy, has been reported to protect ovariectomized animals against H1N1 influenza infections via its anti-inflammatory effects. However, it remains unclear why pregnant women with high gestational estradiol levels are highly susceptible to influe...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2019-01-01
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| Series: | Emerging Microbes and Infections |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2019.1648184 |
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| author | Courtney L. Finch Anding Zhang Martina Kosikova Toshiaki Kawano Marcela F. Pasetti Zhiping Ye Jill R. Ascher Hang Xie |
| author_facet | Courtney L. Finch Anding Zhang Martina Kosikova Toshiaki Kawano Marcela F. Pasetti Zhiping Ye Jill R. Ascher Hang Xie |
| author_sort | Courtney L. Finch |
| collection | DOAJ |
| description | Estradiol, a major female steroid produced during pregnancy, has been reported to protect ovariectomized animals against H1N1 influenza infections via its anti-inflammatory effects. However, it remains unclear why pregnant women with high gestational estradiol levels are highly susceptible to influenza infections. This study was aimed to investigate the effects of pregnancy level of estradiol on female immunity against H5N1 infection in Balb/c mice. A sex-dependent susceptibility to H5N1 infection (higher morbidity and higher mortality) was observed in both pregnant and non-pregnant female mice as compared to male mice. Subcutaneous implantation of estradiol pellets increased serum estradiol concentrations of non-pregnant female mice to the pregnancy level. These mice were protected from H5N1 infection through downregulation of pulmonary pro-inflammatory cytokines. However, the production of virus-specific antibodies after infection was significantly delayed in estradiol-implanted mice when compared to placebos. Virus-specific IgG-secreting and IL-4-secreting cells were also reduced in estradiol-implanted mice. Similarly, lower antibody titers to seasonal vaccine antigens were found in pregnant women as compared to non-pregnant females without hormone usage. Our results indicate that estradiol levels equivalent to those found during pregnancy have divergent effects on female immunity against influenza, highlighting the importance of vaccination during pregnancy to prevent severe influenza infections. |
| format | Article |
| id | doaj-art-fd752c6e299045bfba3ad0722967e183 |
| institution | OA Journals |
| issn | 2222-1751 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj-art-fd752c6e299045bfba3ad0722967e1832025-08-20T02:26:10ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512019-01-01811146115610.1080/22221751.2019.1648184Pregnancy level of estradiol attenuated virus-specific humoral immune response in H5N1-infected female mice despite inducing anti-inflammatory protectionCourtney L. Finch0Anding Zhang1Martina Kosikova2Toshiaki Kawano3Marcela F. Pasetti4Zhiping Ye5Jill R. Ascher6Hang Xie7Division of Viral Products, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD, USADivision of Viral Products, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD, USADivision of Viral Products, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD, USADivision of Viral Products, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD, USADepartment of Pediatrics, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USADivision of Viral Products, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD, USADivision of Veterinary Services, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD, USADivision of Viral Products, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD, USAEstradiol, a major female steroid produced during pregnancy, has been reported to protect ovariectomized animals against H1N1 influenza infections via its anti-inflammatory effects. However, it remains unclear why pregnant women with high gestational estradiol levels are highly susceptible to influenza infections. This study was aimed to investigate the effects of pregnancy level of estradiol on female immunity against H5N1 infection in Balb/c mice. A sex-dependent susceptibility to H5N1 infection (higher morbidity and higher mortality) was observed in both pregnant and non-pregnant female mice as compared to male mice. Subcutaneous implantation of estradiol pellets increased serum estradiol concentrations of non-pregnant female mice to the pregnancy level. These mice were protected from H5N1 infection through downregulation of pulmonary pro-inflammatory cytokines. However, the production of virus-specific antibodies after infection was significantly delayed in estradiol-implanted mice when compared to placebos. Virus-specific IgG-secreting and IL-4-secreting cells were also reduced in estradiol-implanted mice. Similarly, lower antibody titers to seasonal vaccine antigens were found in pregnant women as compared to non-pregnant females without hormone usage. Our results indicate that estradiol levels equivalent to those found during pregnancy have divergent effects on female immunity against influenza, highlighting the importance of vaccination during pregnancy to prevent severe influenza infections.https://www.tandfonline.com/doi/10.1080/22221751.2019.1648184Pregnancy level of estradiolavian influenzahumoral immunityTh2 responsesex-biased |
| spellingShingle | Courtney L. Finch Anding Zhang Martina Kosikova Toshiaki Kawano Marcela F. Pasetti Zhiping Ye Jill R. Ascher Hang Xie Pregnancy level of estradiol attenuated virus-specific humoral immune response in H5N1-infected female mice despite inducing anti-inflammatory protection Emerging Microbes and Infections Pregnancy level of estradiol avian influenza humoral immunity Th2 response sex-biased |
| title | Pregnancy level of estradiol attenuated virus-specific humoral immune response in H5N1-infected female mice despite inducing anti-inflammatory protection |
| title_full | Pregnancy level of estradiol attenuated virus-specific humoral immune response in H5N1-infected female mice despite inducing anti-inflammatory protection |
| title_fullStr | Pregnancy level of estradiol attenuated virus-specific humoral immune response in H5N1-infected female mice despite inducing anti-inflammatory protection |
| title_full_unstemmed | Pregnancy level of estradiol attenuated virus-specific humoral immune response in H5N1-infected female mice despite inducing anti-inflammatory protection |
| title_short | Pregnancy level of estradiol attenuated virus-specific humoral immune response in H5N1-infected female mice despite inducing anti-inflammatory protection |
| title_sort | pregnancy level of estradiol attenuated virus specific humoral immune response in h5n1 infected female mice despite inducing anti inflammatory protection |
| topic | Pregnancy level of estradiol avian influenza humoral immunity Th2 response sex-biased |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2019.1648184 |
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